Gelatin capsule containing hexylresorcinol and a lower polyalkylene glycol



United States Patent GELATIN CAPSULE CONTAINING HEXYLRESOR- (IgTLOL AND A LOWER POLYALKYLENE GLY- William Valentine, Nanuet, and Carl Louis Stearns, Blanvelt, N.Y., assignors to American Cyanamid Company, New York, N.Y., a corporation of Maine No Drawing. Application May 14, 1956 Serial No. 584,457

3 Claims. (Cl. 167-83) This invention relates to a new dosage unit form of hexylresorcinol and to a process of preparing the same.

Hexylresorcinol, 4-hexyl-l,3-dihydroxybenzene, is a heavy liquid which becomes solid upon standing at room temperature. It is considered an effective agent as an anthelmintic, particularly in the treatment of helminths which inhabit the intestinal tract of humans and animals. It has been used against hookworms, pinworms, whipworms and various other helminths. Unfortunately, however, it is very corrosive and is especially irritating to the mucous membranes when given orally. It must, therefore, be coated with some protective agent 'which will prevent contact between the hexylresorcinol and the mouth and throat of the patient.

A number of ways have been suggested to provide suitable forms by which hexylresorcinol may be ingested. Enclosing the hexylresorcinol in a soft gelatin capsule is probably one of the most desirable ways of accomplishing this purpose. It has been found, however, that when hexylresorcinol is encased in a gelatin capsule, discoloration of the capsule and partial destruction of the gelatin coating soon follow so that such capsules have a useful life only a month or so. In addition, the physical nature of hexylresorcinol is such that it is difiicult to place in capsules; and its corrosive nature makes it actually dangerous to handle in the operation.

Efiorts to overcome these diificulties have resulted in proposals to use such materials as olive oil and castor oil as solvents for the hexylresorcinol. These solutions are filled into soft gelatin capsules by conventional encapsulating procedures. It has been found, however, that while this method of encapsulation has substantial advantages over other means, it, too, has a number of disadvantages. The capsules become discolored and the hexylresorcinol solution attacks the soft gelatin capsules so that within about four months the capsules are soft, sticky, have leaked some of the hexylresorcinol and have partially collapsed. As a result, until the present invention, there has been no satisfactory way of dispensing hexylresorcinol; and this valuable drug has not enjoyed widespread usage, especially in the United States. The present invention overcomes the difliculties previously associated with providing a dosage unit form of hexylresorcinol in a surprisingly cheap, easy and effective manner.

We have discovered that hexylresorcinol can be dis solved in certain polyalkylene glycols and the solution can be encapsulated in soft gelatin on conventional capsule making machines and these capsules will remain stable, firm and usable for a long period of time. As a result, this valuable drug can be cheaply encapsulated and distributed in commerce without the ditficulties which have always been associated with the use of this material. The polyalkylene glycols which are suitable for use in this process include the non-toxic liquid polyethylene glycols, polypropylene glycols, and the monocarboxylic fatty acid esters of these glycols. Among those that may be used are included polyoxyethylene glycol, polyoxyethylene-sorbitan, polyoxyethylene-polypropylene glycol, poly- "ice oxyethylene-sorbitan-mono-oleate, and others of like properties. The principal requirement of these polymers is that they be non-toxic and sufiiciently fluid at ordinary temperatures to pump through the metering and filling 5 equipment on the capsule-making machine. The viscosity of these solvents should range from about 10 to 3000 centipoises measured at 23 C. The molecular weight of the suitable polyalkylene glycols varies considerably upon the nature of the glycol and the esterifying groups, but will generally be within the range from 200 to 600. The monomers, ethylene glycol and propylene glycol, are unsatisfactory for the purpose of the present invention, appar ently because soft gelatin capsule-making material is too soluble in these solvents.

In practicing the invention, hexylresorcinol is dissolved in one of the solvents mentioned above at a concentration ranging from about 10 percent to about percent by weight. This solution is then filled into soft gelatin cap sules by conventional encapsulating procedures, the cap sule usually containing about 200 milligrams of hexylresorcinol. Smaller or larger doses ranging from about 10 milligrams for small animals to 1 gram of hexylresorcinol for the larger animals may be used.

Example 50 parts of hexylresorcinol and 50 parts by weight of polyethylene glycol having an average molecular weight of 200 was mixed and heated to 60-65 C. with stirring until the hexylresorcinol had dissolved to give a clear solution. This solution was then filled into soft gelatin capsules on an encapsulating machine such as shown in United States Patent No. 2,690,038Liquid-Filled Capsule Forming Method and Apparatus, issued September 28, 1954, to Stirn et al. These capsules which contained 187 milligrams of hexylresorcinol were placed in a glass bottle and heated at 42 C. for five weeks. There was no apparent damage to the capsules, and they remained full, non-tacky, and attractive.

What we claim is:

1. A dosage unit form of hexylresorcinol suitable for oral administration comprising a gelatin capsule containing from about 10 to 1000 milligrams of hexylresorcinol dissolved in a non-toxic, liquid lower polyalkylene glycol at a concentration of from about 10 percent to 75 percent by weight.

2. A dosage unit form of hexylresorcinol suitable for oral administration comprising a gelatin capsule containing from about 10 to 1000 milligrams of hexylresorcinol dissolved in a non-toxic, liquid polyethylene glycol at a concentration of from about 10 percent to 75 percent by weight.

3. A dosage unit form of hexylresorcinol suitable for oral administration comprising a gelatin capsule containing from about 10 to 1000 milligrams of hexylresorcinol dissolved in a non-toxic, liquid polypropylene glycol at a concentration of from about 10 percent to 75 percent by weight.

References Cited in the file of this patent UNITED STATES PATENTS 2,155,444 Pittenger et al. Apr. 25, 1939 2,775,538 Boskamp Dec. 25, 1956 2,780,355 Palermo et al. Feb. 5, 1957 OTHER REFERENCES Drug and Cos. Ind., vol. 69, No. 3, September 1951, pp. 317 and 378.

The Handbook of Solvents, Scheflan and Jacobs, D. Van Nostrand Co., Inc., N.Y., 1953, p. 602. 

1. A DOSAGE UNIT FORM OF HEXYLRESORCINOL SUITABLE FOR ORAL ADMINISTRATION COMPRISING A GELATIN CAPSULE CONTAINING FROM ABOUT 10 TO 1000 MILLIGRAMS OF HEXYLRESORCINOL DISSOLVED IN A NON-TOXIC, LIQUID LOWER POLYALKYLENE GLYCOL AT A CONCENTRATION OF FROM ABOUT 10 PERCENT TO 75 PERCENT BY WEIGHT. 